1. Field of the Invention
The present invention relates to a WNT10-derived peptide, a composition for improving hair loss and skin conditions using the same, and a composition for treating a WNT10 signal transduction pathway-related disorder and DKK-1 protein-induced disorder using the same.
2. Description of the Related Art
Hair follicle is a peculiar skin organ of mammals, which is developed from the bottom of primitive epidermis into much internal skin layer. The plug of cells known as follicle or dermal papilla exists in the base of the hair follicle (Stenn and Paus, Physiol. Rev., 81: 449 (2002)), and papilla is essential in normal circulation of the hair follicle (Oliver, Embryol. Exp. Morph. 15: 331 (1966); Oliver, Embryol. Exp. Morph. 16: 231 (1967)) and in growth of the hair shaft. The hair shaft is a thread-shaped epithelial cells that are composed of keratin filaments and filament-aggregating proteins tightly attached thereto.
Human hair follows a growth cycle with three distinct phases: anagen, catagen, and telogen phases. The hair growth cycle is regulated by hormones or many growth factors. Severe stress or malnutrition may advance the catagen and telogen phases, leading to severe hair loss (alopecia) (Vladimir A. Botchkarev, American Journal of Pathology, 162 (3): 709-712 (2003)). In male pattern baldness, the hair follicles at the front and top of the scalp are sensitive to androgen, which causes the follicles to miniaturize, thereby resulting in hair loss. Briefly, excessive secretion of androgen activates 5-α reductase which causes testosterone to be converted to dihydrotestosterone (DHT). Subsequently, DHT reduces the number of thick dark terminal hairs by shortening a period of hair growth and by miniaturing hair follicles, leading to hair loss. It has been supposed that about 20% of hair loss women suffer from a few disorders called as “female pattern baldness” which the hair often becomes thinner at the top of the scalp. In addition, hair loss broadens with aging. For example, severe hair loss may be caused from different disorders such as cicatricial alopecia or scar conditions including burns or compression injury. Whatever is the cause, while woman power in the workforce has been enhanced and men have cared about their appearance, hair loss may have remarkable psychological, social and sexual impacts as well as loss of pride and self-respect. Although various medicaments have been used to treat hair loss, they are too expensive or give very different adverse effects among individuals. Additionally, it is necessary to take these drugs in a constant manner. In this connection, it is one of serious drawbacks that hair loss may be caused by stopping them. Meanwhile, another demerit is that their efficacies and side effects may be quitely different between individuals.
Raw materials utilized in cosmetic products have the advantage of being inexpensive, whereas do not give good results since they are composed of plant extract-derived components. To overcome shortcomings in view of biostability, efficacy or cost, there has been developed a method that WNT10-derived peptides having activities identical to a natural-occurring WNT10 may be produced in an inexpensive manner by a chemical synthesis method, and a nano peptide product having a superior efficacy and skin permeability using a nanosome technology, compared with a whole protein. The peptide permits to induce the proliferation and differentiation of stem cell present in hair follicle on skin to produce hair root, leading to develop new hair follicle. In addition, the peptide allows activation of WNT-β-catenin signal pathway to express genes inducing hair growth even under conditions that WNT10 pathway is inactivated by DKK-1, a hair loss gene, produced by DHT. Furthermore, the peptide effectively facilitates anagen during which hair growth is active, and potently inhibits transition of anagen to catagen in hair follicle cycle caused by various environmental factors, resulting in inhibition of hair loss. In addition, the peptide shows beneficial effects on growth and healthy of normal hair through supplying nutrients to hair. It has been known up to now that two commercial drugs (minoxidil and finasteride) may delay only additional hair loss. However, no actual medicaments may have been useful to induce regeneration of new hair follicle in practice. Many scalp cosmetics for preventing hair loss have been commercially available in the market, for example including: (a) a product including a plant extract derived from sophora, hot pepper, Swertia herb, Morus alba, mulberry leaf, ginseng, licorice, peony, foxglove, fennel, Japanese cornel, garlic, and so forth; (b) a composition containing xanthines and growth hormones for not only improving cellular metabolism suppressed by excess dihydrotestosterone (DHT) but also facilitating hair growth through hair loss inhibition and hair regeneration induced by growth hormones; (c) a product containing minerals, vitamins and extracts of green tea, rosemary, mugwort or licorice, which supplies nutrients to the scalp and hair for preventing hair loss and promoting hair growth; and (d) a male pattern baldness product mixing the substances such as vitamin B, vitamin C, vitamin D, vitamin E, nicotinic acid, pantothenic acid, biotin, folic acid, etc. with plant extracts, which inhibits 5-α reductases to suppress production of DHT during androgen metabolism and to help hair metabolism by have been developed. However, they have hardly influence on the production of new hair. As another example, a research group of the Jikei University School of Medicine in Tokyo, Japan has developed the product using corosolic acid known to be effective in diabetes, which inhibits 5-α reductases and exhibits an excellent effect on hair growth.
Many factors are associated with each other in the growth and degeneration of hair. For hair production, the present researchers have studied serial growth factors having an activity for: (a) promoting proliferation of keratinocyte which is most important for hair root production; (b) inducing differentiation of hair; (c) supplying nutrients to the vicinity of hair; and (d) activating vascular endothelial growth factors. Of them, human-derived WNT10 specifically affects hair development by transferring a signal to a cell. WNT10 signal transduction pathway is activated by an interaction between secreted WNT10 protein and Frizzled protein which is a receptor thereof. In this connection, LDL receptor-related proteins (LRP5 and LRP6) function as a co-receptor (Clin Cancer Res 2007; 13 (14) Jul. 15, 2007, WNT Signaling Pathway and Stem Cell Signaling Network). Downstream effects in WNT10 signal transduction pathway include participation of Axin-β-catenin-GSK3 β complex through activation of DVL (Disheveled) protein and Akt (Fukumoto et al., J. Biol. Chem., 276: 17479-17483 (2001)). Afterwards, GSK3 β is inactivated by phosphorylation, resulting in inhibition of phosphorylation and degradation of β-catenin. Accumulated β-catenins are translocated to a nucleus and then interact with transcription factors of the lymphoid enhancer factor-T cell factor (LEF-TCF), permitting to induce transcription of target genes. The resulting proteins may be a critical role for hair growth and differentiation, and allow new hair cell to be produced. Furthermore, they decrease activities of DHT produced by male hormone (androgen) to suppress hair loss.
Throughout this application, various patents and publications are referenced and citations are provided in parentheses. The disclosure of these patents and publications in their entities are hereby incorporated by references into this application in order to more fully describe this invention and the state of the art to which this invention pertains.